Endocannabinoidome

Abstract

The classical definition of the endocannabinoid system (ECS), at the turn of the century, was that of a complex pleiotropic system composed by: (1) the two cannabinoid receptors (CB 1 and CB 2 ); (2) their endogenous ligands, the ‘endocannabinoids’ (EC) and (3) the five enzymes believed at that time to be uniquely responsible for EC biosynthesis and degradation. However, studies carried out during the last 10 years have revealed the potential existence of a high degree of redundancy for both the molecular targets and metabolic routes, and corresponding enzymes, of the ECs. Therefore, these new discoveries suggested that the time had come to expand our view of the ECS. In fact, other bioactive long chain fatty acid amides were identified, and their biosynthesis, inactivation and function investigated. Since this plethora of novel mediators has something more than a few chemical features in common with ECs, the name of ‘endocannabinoidome’ (eCBome) was proposed. Key Concepts The endocannabinoid system is an ever‐expanding pleiotropic signalling system with key role in several physiopathological conditions. Studies carried out during the last 10 years have revealed the potential existence of a high degree of redundancy for both the molecular targets and metabolic routes, and corresponding enzymes, of the endocannabinoids. Several N ‐acyl‐ethanolamines (NAEs), monoacylglycerols, N ‐acyl amino acids, N ‐acyldopamines/taurines/serotonines were suggested to be part of this system. These endocannabinoid‐like molecules may activate other molecular targets independently from cannabinoid receptors. All these recent findings together with the discovery of new endocannabinoid‐like molecules have led us to expand the classical view of the eCB system and to look at it as the ‘endocannabinoidome’.

The Endocannabinoid System: A Bridge between Alzheimer’s Disease and Gut Microbiota

“…Interestingly, CB 1 and CB 2 are not the only receptors whose activity are responsive to AEA and 2-AG, as both ligands are able to modulate other GPCRs such as GPR-18, GPR-55 and GPR-119, the thermosensitive transient receptor potential cation channels, such as the vanilloid type-1 (TRPV1), as well as peroxisome proliferator-activated receptor-α and -γ (PPAR-α and -γ) [ 39 ]. The identification of a continuous increasing number of bioactive long chain fatty acid amides having eCB-like properties, such as other NAEs, including N -palmitoylethanolamine (PEA) and N -oleylethanolamine (OEA) or N -acyl amino acids/dopamine/taurine/serotonines, has allowed to expand the concept of the eCB system towards the “endocannabinoidome” (eCBome) [ 42 ]. This new plethora of bioactive compounds share with eCBs metabolic pathways and molecular targets, not only CB 1 and CB 2 [ 20 , 43 ], but also GPR-55, TRPV1 and PPAR [ 44 , 45 ] mimicking the physiological features of eCBs.…”

The Endocannabinoidome

“…There are few studies published about the endocannabinoidome system. It has been suggested that these compounds work via a mechanism that does not involve the traditional endocannabinoid receptors, which may allow them to bypass the current problems associated with manipulating the endocannabinoid system to treat TBI (Arturo & Fabiana, 2018). Experimentation to this end has resulted in conflicting answers with no clear path forward.…”

“…1). Future experiments will involve testing the neuroprotective properties of other endocannabinoidome ligand families in TBI mouse models such as N-arachidonoyldopamines, N-acyl-serotonins, N-acyltaurines, and other Nacyl amino acids members (Arturo & Fabiana, 2018). The dependency of the traditional CB receptors of new endocannabinoidome ligands can be tested by using the same method as the PalmS study: using CB1, CB2, and TRPV1 antagonists, along with receptor knockout models to see if there are any effects on the ability of the molecule to mitigate TBI damage (Mann et al, 2015;Fig.…”

Healthy cats tolerate long-term daily feeding of Cannabidiol

“…As such it has made for a promising candidate in many therapeutic areas such as pain management in osteoarthritis, epilepsy, Alzheimer’s disease, multiple sclerosis, and anxiety in humans ( 3 ), benefits which may translate to animals ( 4 ). CBD, therefore, shows efficacy for a wide variety of conditions which act via numerous pathways linked to the endocannabinoid system ( 5 ), and these have been collectively labeled the endocannabinoidome ( 6 ), indicating there are several potential modes of action. These include, but are not limited to, G-protein-coupled cannabinoid receptors type 1 and 2 (CB1 and CB2), transient receptor vanilloid type-1 (TRPV1) channel, G-protein-coupled receptor 55 (GPR55) or 119 (GPR119), and peroxisome proliferator-activated receptors (PPAR)α and γ ( 5 ).…”